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Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1

Nature Immunology volume 7, pages 517–523 (2006)Cite this article

Abstract

The elimination of viruses and tumors by natural killer cells is mediated by specific natural killer cell receptors. To study the in vivo function of a principal activating natural killer cell receptor, NCR1 (NKp46 in humans), we replaced the gene encoding this receptor (Ncr1) with a green fluorescent protein reporter cassette. There was enhanced spread of certain tumors in 129/Sv but not C57BL/6 Ncr1gfp/gfp mice, and influenza virus infection was lethal in both 129/Sv and C57BL/6 Ncr1gfp/gfp mice. We noted accumulation of natural killer cells at the site of influenza infection by tracking the green fluorescent protein. Our results demonstrate a critical function for Ncr1 in the in vivo eradication of influenza virus.

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Figure 1: Ncr1gfp expression in NK cells.
Figure 2: NK cell–specific Ncr1gfp expression.
Figure 3: Reduced clearance of tumor cells in vivo.
Figure 4: Lethal influenza infection in 129/Sv Ncr1gfp/gfp mice.
Figure 5: NK cells accumulate at the site of influenza infection.
Figure 6: Strain-specific NCR1 functions.

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Acknowledgements

Supported by the Israel Science Foundation (O.M.), the Binational Science Foundation (O.M.), the Israel Ministry of Health and the European Commission (LSHC-CT-2002-518178 to O.M.).

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Authors and Affiliations

  1. The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel

    Roi Gazit, Raizy Gruda, Moran Elboim, Tal I Arnon, Gil Katz, Hagit Achdout, Jacob Hanna & Ofer Mandelboim

  2. Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva, 84105, Israel

    Udi Qimron, Guy Landau & Angel Porgador

  3. Virology Department, The Hebrew University, Hadassah Medical Center, Jerusalem, 91120, Israel

    Evgenia Greenbaum & Zichria Zakay-Rones

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  1. Roi Gazit
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Correspondence to Ofer Mandelboim.

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Supplementary information

Supplementary Figure 1

Generation of Ncr1gfp/gfp mice. (PDF 541 kb)

Supplementary Figure 2

Ncr1gfp expression in NK cells after PGK-neor excision in 129/sv mice. (PDF 402 kb)

Supplementary Figure 3

NK cell-specific Ncr1gfp expression in 129/sv mice after PGK-neor excision. (PDF 401 kb)

Supplementary Figure 4

C57BL/6 mice express Ncr1gfp in NK cells. (PDF 426 kb)

Supplementary Figure 5

NK cell-specific Ncr1gfp expression in C57BL/6 mice. (PDF 421 kb)

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Gazit, R., Gruda, R., Elboim, M. et al. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nat Immunol 7, 517–523 (2006). https://doi.org/10.1038/ni1322

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